Empowering lung cancer treatment: Harnessing the potential of natural phytoconstituent-loaded nanoparticles.

Lung cancer, the second leading cause of cancer-related deaths, accounts for a substantial portion, representing 18.4% of all cancer fatalities. Despite advances in treatment modalities such as chemotherapy, surgery, and immunotherapy, significant challenges persist, including chemoresistance, non-specific targeting, and adverse effects. Consequently, there is an urgent need for innovative therapeutic approaches to overcome these limitations. Natural compounds, particularly phytoconstituents, have emerged as promising candidates due to their potent anticancer properties and relatively low incidence of adverse effects compared to conventional treatments. However, inherent challenges such as poor solubility, rapid metabolism, and enzymatic degradation hinder their clinical utility. To address these obstacles, researchers have increasingly turned to nanotechnology-based drug delivery systems (DDS). Nanocarriers offer several advantages, including enhanced drug stability, prolonged circulation time, and targeted delivery to tumor sites, thereby minimizing off-target effects. By encapsulating phytoconstituents within nanocarriers, researchers aim to optimize their bioavailability and therapeutic efficacy while reducing systemic toxicity. Moreover, the integration of nanotechnology with phytoconstituents allows for a nuanced understanding of the intricate molecular pathways involved in lung cancer pathogenesis. This integrated approach holds promise for modulating key cellular processes implicated in tumor growth and progression. Additionally, by leveraging the synergistic effects of phytoconstituents and nanocarriers, researchers seek to develop tailored therapeutic strategies that maximize efficacy while minimizing adverse effects. In conclusion, the integration of phytoconstituents with nanocarriers represents a promising avenue for advancing lung cancer treatment. This synergistic approach has the potential to revolutionize current therapeutic paradigms by offering targeted, efficient, and minimally toxic interventions. Continued research in this field holds the promise of improving patient outcomes and addressing unmet clinical needs in lung cancer management.

Modification and Functionalization of Polymers for Targeting to Bone Cancer and Bone Regeneration.

Bone is one of the most complex, inaccessible body structures, responsible for calcium storage and haematopoiesis. The second highest cause of death across the world is cancer. Amongst all the types of cancers, bone cancer treatment modalities are limited due to the structural complexity and inaccessibility of bones. The worldwide incidence of bone diseases and bone defects due to cancer, infection, trauma, age-related bone degeneration is increasing. Currently different conventional therapies are available for bone cancer such as chemotherapy, surgery and radiotherapy, but they have several disadvantages associated with them. Nanomedicine is being extensively researched as viable therapeutics to mitigate drug resistance in cancer therapy and promote bone regeneration. Several natural polymers such as chitosan, dextran, alginate, hyaluronic acid, and synthetic polymers like polyglycolic acid, poly(lactic-co-glycolic acid), polycaprolactone are investigated for their application in nanomedicine for bone cancer treatment and bone regeneration. Nanocarriers have shown promising results in preclinical experimental studies. However, they still face a major drawback of inadequate targetability. The paper summarizes the status of research and the progress made so far in modifications and functionalization of natural polymers for improving their site specificity and targeting for effective treatment of bone cancer and enhancing bone regeneration.

Exploring Nose to Brain Nano Delivery for Effective Management of Migraine.

Migraine is a disabling disease characterized by severe throbbing headaches. Patients demand quick relief from this pain. The presence of the blood-brain barrier does not permit the drug to penetrate the brain effectively. Administration of conventional anti-migraine medications via oral route leads to erratic absorption of drugs. Delayed gastric emptying is also responsible for the ineffective absorption of the drug. Migraine-induced nausea and vomiting further limit patient compliance to oral medication. Other limitations associated with the oral route include extensive first-pass metabolism, slow onset of action, inability to cross the blood-brain barrier, requirement of a large amount of dose/dosage, and frequent administration. The anti-migraine drugs used in migraine, such as triptans, are therapeutically effective but have low bioavailability on oral administration. Also, these drugs are associated with several cardiovascular complications. The oral dose of most antimigraine drugs, oral triptans, Ergotamine, NSAIDs, and CGRP antagonists is quite high because of their poor bioavailability. As a result, these drugs are associated with several side effects. This aspect necessitates the need to develop a dosage form that can deliver drugs directly to the brain, thereby reducing the dose. Invasive techniques to deliver these therapeutics to the brain do exist. However, they are painful, require expert assistance, and are not a cost-effective approach for migraine treatment. These limitations demand the development of a novel non-invasive approach that is safe, efficacious, and has high patient compliance. According to reports, it is possible to target the brain tissue by administering the drug intranasally using the olfactory and the trigeminal pathway. This route is non-invasive, avoids first-pass metabolism, eliminates nausea and vomiting, helps reduce dose, and thus helps achieve increased patient compliance. Some factors like solubility, the lipophilicity of the drug, mucociliary clearance, and enzymatic degradation hinder the bioavailability of the drug by nasal route. Therefore, there is a grave need to develop novel nasal formulations with prolonged nasal residence time, which can modulate pharmacokinetics for adequate therapeutic response and render efficient yet robust brain targeting. Considering these challenges, developing an efficient intranasal dosage form is necessary. This review gives a brief overview of all the novel carriers reported for improving the treatment of migraine. Nanocarrier-based delivery systems like in situ gels, microemulsion, nanoemulsion, nanoparticles, vesicular systems, micelles, and microspheres used in nose to brain delivery of migraine therapeutics are also discussed in the article.

Mannose-conjugated chitosan nanoparticles for delivery of Rifampicin to Osteoarticular tuberculosis.

Tuberculosis (TB) is a potentially fatal contagious disease and is a second leading infectious cause of death in the world. Osteoarticular TB is treated using standard regimen of 1st and 2nd line anti-tubercular drugs (ATDs) for extensive period of 8-20 months. These drugs are commonly administered in high doses by oral route or by intravenous route, because of their compromised bioavailability. The common drawbacks associated with conventional therapy are poor patient compliance due to long treatment period, frequent and high dosing, and toxicity. This aspect marks for the need of formulations to eliminate these drawbacks. MTB is an intracellular pathogen of mononuclear phagocyte. This attribute makes nanotherapeutics an ideal approach for MTB treatment as macrophages capture nano forms. Polymeric nanoparticles are removed from the body by opsonization and phagocytosis, which forms an ideal strategy to target macrophage containing mycobacteria. To further improve targetability, the nanoparticles are conjugated with ligand, which serves as an easy substrate for the receptors present on the macrophage surface. The purpose of present work was to develop intra-articular injectable in situ gelling system containing polymeric nanoparticles, which would have promising advantages over conventional method of treatment. The rationale behind formulating nanoparticle incorporated in situ gel-based system was to ensure localization of the formulation in intra-articular cavity along with sustained release and conjugation of nanoparticles with mannose as ligand to improve uptake by macrophages. Rifampicin standard ATD was formulated into chitosan nanoparticles. Chitosan with 85% degree of deacetylation (DDA) and sodium tripolyphosphate (TPP) as the crosslinking agent was used for preparing nanoparticles. The percent entrapment was found to be about 71%. The prepared nanoparticles were conjugated with mannose. Conjugation of ligand was ascertained by performing Fourier transformed infrared spectroscopy. The particle size was found to be in the range of 130-140 nm and zeta potential of 38.5 mV. Additionally, we performed scanning electron microscopy to characterize the surface morphology of ligand-conjugated nanoparticles. The conjugated chitosan nanoparticles were incorporated into in situ gelling system comprising Poloxamer 407 and HPMC K4M. The gelling system was evaluated for viscosity, gelling characteristics, and syringeability. The drug release from conjugated nanoparticles incorporated in in situ gel was found to be about 70.3% at the end of 40 h in simulated synovial fluid following zero-order release kinetics. Based on the initial encouraging results obtained, the nanoparticles are being envisaged for ex vivo cellular uptake study using TB-infected macrophages.

Colorectal Cancer Management by Herbal Drug-Based Nanocarriers: An Overview.

Colorectal cancer is the third most common cancer in the world, affecting both men and women, and it is one of the leading causes of cancer related deaths worldwide. Current treatment modalities employed for colorectal cancer management have their own share of drawbacks, such as toxicity due to nonspecific action and chemoresistance that may develop during treatment. The quest and pursuit for newer drugs which can overcome these drawbacks has led to extensive research on plant derived phytoconstituents. Herbal molecules are known to have promising therapeutic efficacy and less toxicity as compared to the current chemotherapeutic drugs of allopathic regimen. However most of these herbal molecules have low bioavailability as a result their therapeutic efficacy gets compromised. Integration of modern delivery approaches with these herbal molecules and presenting them in the form of nanocarriers will help alleviate these drawbacks. This review describes herbal drugs that have potential for treatment of colorectal cancer and nanotechnology strategies widely investigated for the delivery of these herbal molecules. Targeted delivery methods include use of such components as polymeric nanoparticles, liposomes, dendrimers, magnetic nanoparticles, solid lipid nanoparticles, and nanoemulsions. The paper also discusses in detail the formulation aspects of herbal nanocarriers, their design development, and preclinical assessment.

In Vivo Evaluation of 5-ASA Colon-Specific Tablets Using Experimental-Induced Colitis Rat Animal Model.

Colonic drug delivery is intended not only for local treatment in inflammatory bowel disease (IBD) but also for systemic delivery of therapeutics. Intestinal myeloperoxidase (MPO) determination could be used to estimate the average level of inflammation in colon as well as to determine the efficacy of drugs to be used in the treatment of inflammatory bowel diseases or study the specificity of dosage forms to be used for colonic targeting of anti-inflammatory drugs. Colonic prodrug sulfasalazine (SASP) gets metabolized to give 5-aminosalicylic acid (5-ASA), which is the active portion of SASP. However, when given orally, 5-ASA is absorbed in upper part of gastrointestinal tract (GIT) and not made available in colon. In the present study, colon-targeted delivery of 5-ASA was achieved by formulating tablets with two natural polymers namely guar gum and pectin using compression coating method. Colonic specificity of 5-ASA tablets (prepared using guar gum and pectin as polymers) was evaluated in vitro using simulated fluids mimicking in vivo environment as well as in vivo method using chemically (2,4,6-trinitrobenzenesulfonic acid and acetic acid)-induced colitis rat model. Both colon-specific formulations of 5-ASA (guar gum and pectin) were observed to be more effective in reducing inflammation in chemically induced colitis rat models when compared to colon-specific prodrug sulfasalazine as well as conventional 5-ASA administered orally.